Drivers of solid waste collection costs. Empirical evidence from Italy.

The paper analyses the factors that determine the solid waste collection costs. Studying a sample of Italian municipalities, the research estimates the collection costs of different types of waste: paper and paperboard, multimaterial (glass, plastic, metal), organic, residual undifferentiated waste. The findings show that the economies of scale and the cost drivers differ across the types of waste

Efficient delivery of DNA to dendritic cells mediated by influenza virosomes.

In an attempt to enhance the immunological efficacy of DNA-based vaccines, we have investigated a new biological means for delivering target gene DNA directly to professional antigen presenting cells (APC), such as the dendritic cells (DC), which are ultimately responsible for the antigen presentation and the primary activation of the immune system. For this purpose we investigated influenza virosomes (IRIV) with assembled DNA as a possible biological carrier for targeting the APC in vivo and in vitro. By cytofluorimetric analysis of the draining lymph nodes of Balb/c mice which had received (by intranasal (in.) administration) FITC-labeled DNA assembled with IRIV, we detected a significant labeled DNA uptake in a subset of lymph node deriving cells expressing DC surface markers. Subsequent mRNA analysis of these lymph nodes showed that the trans-gene delivered by the virosomes was effectively expressed as mRNA. Finally, a further cytofluorimetric analysis performed on human DC-enriched-PMBC, infected in vitro with labeled DNA/IRIV lead to the conclusion that the majority of APC (DC, B lymphocytes and CD16+ cells) are able to incorporate the labeled DNA transported by the construct. These findings suggest that the virosome is an efficient delivery system for testing infectious, as well as anti-cancer, DNA-based vaccine research

Personality patterns of headache sufferers.

One hundred and sixty-seven subjects (91 females and 76 males) aged 18 to 55 and suffering from recurrent headache, daily headache, and cluster headache, were studied. In order to collect detailed information about their clinical as well as social and environmental conditions, a multi-page card was used which had been specially prepared for this purpose. The patients' personality patterns were assessed by the following methods: MMPI (the Hs, Hy, D, and Ma scales, in particular); EPQ (Eysenck Personality Questionnaire); and AS IPAT (Cattel's Anxiety Scale). The statistical analysis of the data obtained made it possible to define the personality patterns of both male and female subjects and then to differentiate between them in relation to the various types of headache. Furthermore, possible relationships between personality traits and headache suffering were investigated. If the personality patterns of females seem to have existed prior to the disease, those of males raise some questions. In cluster patients, in particular, the age of onset seems to be related to certain personality traits; in patients with daily headache, by contrast the association between the duration and severity of the disorder appears to play a major trigger role. Some of these correlations do not have a linear character and suggest new working hypotheses that go beyond the limits of standard correlations

Immunization with Toscana virus N-Gc proteins protects mice against virus challenge

Toscana virus (TOSV) is an emerging virus, circulating in the Mediterranean area, that is responsible for aseptic meningitis, meningoencephalitis, and encephalitis. The development of a vaccine that could provide complete protection from TOSV infection is needed. In this study we investigated the capacity of TOSV structural proteins, nucleocapsid protein N and the two Gc and Gn glycoproteins, produced as recombinant proteins, in an animal model. In particular, we investigated their role in inducing specific and protective immune responses against virus infection. Mice were immunized intraperitoneally using TOSV antigens singly or in combination. The results show that only the N-Gc combination was able to protect 100% of animals from a lethal challenge with a neurovirulent strain of TOSV. This potential vaccine induces high serum antibody titres with neutralizing activity and it is safe for animals. Moreover, immunization induces a virus specific cell-mediated immune response, in particular a CD8+ T cell response associated with a marked expression of interferon gamma. These results indicate that the N+Gc viral antigen combination could be useful for future development of a vaccine controlling the spread of this emerging virus that could pose a new threat for humans

Cetuximab +/- chemotherapy enhances dendritic cell-mediated phagocytosis of colon cancer cells and ignites a highly efficient colon cancer antigen-specific cytotoxic T-cell response in vitro.

Cetuximab is a human/mouse chimeric IgG1 monoclonal antibody (mAb) to epidermal growth factor receptor, approved for colorectal carcinoma treatment in combination with chemotherapy. The immune-mediated effects elicited by its human fraction of crystallization moiety might critically contribute to the overall anti-tumor effectiveness of the antibody. We therefore investigated cetuximab ability to promote colon cancer cell opsonization and phagocytosis by human dendritic cells (DCs) that are subsequently engaged in antigen-cross presentation to cytotoxic T-lymphocyte (CTL) precursors. Human colon cancer cell lines were evaluated for susceptibility to DC-mediated phagocytosis before and after treatment with chemotherapy ± cetuximab in vitro. Human DCs loaded with control or drug-treated cetuximab-coated colon cancer cells were used to in vitro generate cytotoxic T cell clones from peripheral blood mononuclear cells of human leucocyte antigen-A(*)02.01(+) donors. T-cell cultures were characterized for immune-phenotype and tumor-antigen specific CTL activity. The results confirmed that treatment of tumor cells with irinotecan + L-folinate + 5-flurouracil (ILF) or with gemcitabine + ILF increased tumor antigen expression. Moreover, malignant cells exposed to chemotherapy and cetuximab were highly susceptible to phagocytosis by human DCs and were able to promote their activation. The consequent DC-mediated cross-priming of antigens derived from mAb-covered/drug-treated cancer cells elicited a robust CTL anti-tumor response. On the basis of our data, we suggest a possible involvement of CTL-dependent immunity in cetuximab anti-cancer effects

5-fluorouracil-based chemotherapy enhances the antitumor activity of a thymidylate synthase-directed polyepitopic peptide vaccine.

DNA synthesis, is often overexpressed in cancer cells. Some chemotherapeutic agents, such as 5-fl uorouracil (5-FU), act by inhibiting TS expression. We evaluated whether a novel 28-amino acid multiepitope peptide, TS/PP, that contains the sequences of three TS-derived epitopes with binding motifs for HLA-A(*)02.01 could induce a TS-directed cytotoxic Tlymphocyte (CTL) response with antitumor activity. Methods: TS/PP peptide immunologic activity in CTL lines derived from human leukocyte antigen (HLA)-A(*)02.01 + peripheral blood mononuclear cells (PBMCs) was tested in the presence of interleukin-2 and autologous TS/PP peptide-loaded dendritic cells. Immunologic and antitumor activities of TS/PP and its toxicity were also evaluated in vivo in HLA-A(*)02.01 transgenic (HHD) mice that were vaccinated with TS/PP, control, or TS-peptide cocktail and treated with or without 5-FU chemotherapy. The mice were also inoculated subcutaneously with TS-expressing EL-4/HHD lymphoma cells to assess immune response against these tumor cells. Results: TS/PP-specifi c CTL lines showed a TS-multiepitopic specifi city and were able to kill TS + /HLA-A(*)02.01 + breast and colon carcinoma cells. The killing ability against target cells previously exposed to sublethal doses of 5-FU was statistically signifi cantly greater than against untreated target cells (43.5% versus 26.5% at 25/1 effector to target ratio [Difference {diff} = 17.0]; 95% confi dence interval [CI] = 12.6 to 20.4) for MDA-MB-231 breast carcinoma cells and 73.5 versus 48.5 (diff = 25.0; 95% CI = 16.2 to 33.8) for the SW-1463 colon carcinoma cells. HHD mice vaccinated with TS/PP manifested a TS-peptide-specifi c CTL response with no sign of autoimmunity or toxicity. Furthermore, treatment of these mice with 5-FU delayed or prevented the occurrence of tumors formed by inoculation with autologous (TS + )EL-4/HHD lymphoma cells. Conclusions: The multiepitopic TS/PP vaccine induces a tumor-specifi c immune response in mice and is especially potent when used in combination with 5-FU-based chemotherapy

Toscana virus infects dendritic and endothelial cells opening the way for the central nervous system

Toscana virus (TOSV) is a Phlebovirus responsible for human neurological infections in endemic Mediterranean areas. The main viral target is the central nervous system, with viremia as a way of dissemination throughout the host. This study was aimed at understanding the spread of TOSV in the host by identifying the cell population infected by the virus and the vehicle to the organs. In vivo studies provided evidence that endothelial cells are infected by TOSV, indicating their potential role in the diffusion of the virus following viremic spread. These results were further confirmed in vitro. Human peripheral mononuclear blood cells were infected with TOSV; only monocyte-derived dendritic cells were identified as susceptible to TOSV infection. Productive viral replication was then observed in human monocyte-derived dendritic cells (moDCs) and in human endothelial cells by recovery of the virus from a cell supernatant. Interleukin-6 was produced by both cell types upon TOSV infection, mostly by endothelial cells, while moDCs particularly expressed TNF-α, which is known to induce a long-lasting decrease in endothelial cell barrier function. These cells could therefore be implicated in the spread of the virus in the host and in the infection of tissues that are affected by the disease, such as the central nervous system. The identification of in vitro and in vivo TOSV cell targets is an important tool for understanding the pathogenesis of the infection, providing new insight into virus-cell interaction for improved knowledge and control of this viral disease